Document Detail


Mechanism of inactivation of gamma-aminobutyric acid-alpha-ketoglutaric acid aminotransferase by 4-amino-5-halopentanoic acids.
MedLine Citation:
PMID:  7225323     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
(S)-4-Amino-5-halopentanoic acids were previously shown to irreversibly inhibit pig brain gamma-aminobutyric acid--alpha-ketoglutaric acid aminotransferase, and a mechanism for the inactivation was proposed (Silverman, R. B., & Levy M. A. (1980) Biochem. Biophys. Res. Commun. 95, 250). Evidence is presented to show that these compounds are mechanism-based inactivators, and experiments are described to elucidate their mechanism of action. The enzyme must be in the pyridoxal phosphate form for inactivation to occur, the gamma proton of the inactivators is removed in a rate-determining step, and one fluoride ion is released from 4-amino-5-fluoropentanoic acid per active site labeled. The change in the optical spectrum of the enzyme during inactivation suggests that the coenzyme is converted into the pyridoxamine phosphate form. Every turnover of inactivator leads to an inactivation event, i.e., the partition ratio is zero.
Authors:
R B Silverman; M A Levy
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  20     ISSN:  0006-2960     ISO Abbreviation:  Biochemistry     Publication Date:  1981 Mar 
Date Detail:
Created Date:  1981-07-20     Completed Date:  1981-07-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1197-203     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
4-Aminobutyrate Transaminase / antagonists & inhibitors*
Amino Acids / pharmacology*
Animals
Brain / enzymology
Deuterium
Isotope Labeling
Kinetics
Spectrophotometry
Structure-Activity Relationship
Swine
Transaminases / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
NS 15703/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 7782-39-0/Deuterium; EC 2.6.1.-/Transaminases; EC 2.6.1.19/4-Aminobutyrate Transaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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